For the past 28 years, we have been following and studying a group of children at high risk for schizophrenia in order to try to understand why some became schizophrenic and why some have successful lives. We have proposed a "two-hit' theory of the etiology of schizophrenia. The theory suggests that the fiat hit consists of a genetic predisposition to abnormal neural development during the second trimester of gestation and that the second hit is environmental. The environmental hit consists of either 1) brain damage caused by delivery complications or 2) stressful early family rearing conditions. The nature of the second hit may help determine type of course of the illness. In addition to the 28-year study of the high risk children, we propose investigations of birth cohorts in Copenhagen and Helsinki to study the role of disturbances of gestation and of delivery in the etiology of schizophrenia and in the determination of type of course of the illness. In an additional research project, we are testing the basic assumption that the first genetic hit results in disturbed fetal neural development. In this study we are completing anatomical, immunocytochemical and molecular neurobiological studies of targeted areas of the cerebral cortex and diencephalon of the brains of second-trimester aborted fetuses of schizophrenic women and controls. Plans for training of the PI include gaining familiarity with the laboratory procedures for neuroanatomy, immunocytochemical and molecular neurobiology research.